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Objectives:Redox imbalance and genotoxic damage are commonly observed in β thalassaemic patients. The aim of this study was to assess the role of anaemia in oxidative and genotoxic damage in regularly transfused thalassaemic patients, undergoing iron chelation therapy. Methods:We studied the relationships of haematological, biochemical and clinical parameters with oxidative (reactive oxygen species and 8-oxo-7,8-dihydro-2′-deoxyguanosine) and genotoxic biomarkers (Comet assay and cytokinesis-block micronucleus test) in blood samples from 105 patients. To reduce the early effect of redox-active iron, samples were collected when pharmacokinetics of the iron chelators ensured their maximum effectiveness. The transfusion regimen, cardiac and hepatic magnetic resonance imaging T2 were evaluated to characterize the patient cohort. Labile plasma iron (LPI) was also assayed. Results:Haemoglobin level had a significant effect on ROS, %DNA in the tail and micronuclei-micronucleated cell frequency (p < 0.05). Higher Hb values reduced redox imbalance. LPI, detectable in 50.5% of patients, was related to the number of apoptotic and necrotic lymphocytes (p = 0.03), demonstrating the cytotoxic effect of iron. Discussion:The results highlight that an adequate transfusion regimen is essential to limit oxidative and genotoxic damage in β-thalassemic patients undergoing chelation therapy. Conclusion:Owing to the higher risk of cancer in the thalassaemic cohorts, specific genotoxicity/oxidative biomarkers should be monitored in order to ameliorate and formulate more personalized disease management. [ABSTRACT FROM AUTHOR]

This study aimed to determine the feasibility, reproducibility, and reliability of the multiecho T*2 Magnetic resonance imaging technique at 3 T for myocardial and liver iron burden quantification and the relationship between T*2 values at 3 and 1.5 T. Thirty-eight transfusion-dependent patients and 20 healthy subjects were studied. Cardiac segmental and global T*2 values were calculated after developing a correction map to compensate the artifactual T*2 variations. The hepatic T*2 value was determined over a region of interest. The intraoperator and interoperator reproducibility for T*2 measurements at 3 T was good. A linear relationship was found between patients' R [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted by the author on thalassaemic patients with anaemia-induced hypoxia. Topics discussed include stabilization of HIF1α subunits and Glut1 levels by iron chelation therapy in transfused patients, prolonged hypoxic conditions of untransfused patients due to low oxygen tension and suggests for blood transfusion to block the homeostatic response to hypoxia, gastrointestinal iron absorption and bone marrow activity.

We analyzed the prevalence of α-thalassemia mutations in 298 subjects from Eastern Sicily (Italy) with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), normal HbA2 and HbF, and normal serum iron. In 131 subjects (43.9%) we found six different genotypes of α-thalassemia: -α3.7/αα (36.6%), -α3.7/-α3.7 (27.5%), –MED/αα (10.0%), -α20.5/αα (9.1%), αHphIα/αα (8.4%), αHphIα/αHphIα (6.1%), and -α3.7/αHphIα (2.3%). Our data underline that in Eastern Sicily populations, the molecular screening of α-thalassemia mutations and/or deletions may be useful to better characterize the clinically asymptomatic subjects with a slightly reduced MCV and MCH and normal iron status. [ABSTRACT FROM AUTHOR]

Objective: Endocrine complications characterised patients with β thalassaemia (βT). In particular, thyroid dysfunction occurs frequently in βT major, but its long-term natural history is poorly understood., Design: A total of 72 βT patients were followed for 8 years. The incidence of thyreopathies, defined as the primary study endpoint, was assessed. The aim of this study was to analyse the prognostic role of ferritin for thyreopathies in patients with major and intermedia βT. The power of different iron chelators to treat iron overload and to prevent or reverse thyreopathies was also assessed., Methods: Patients were treated with chelators with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying thyroid dysfunction in thalassaemic patients. Kaplan-Meier curves were generated to assess incidence of thyreopathy. Adjusted risk estimates for thyreopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis., Results: PATIENTS WITH THYROID DYSFUNCTION WERE CHARACTERISED BY HIGHER FERRITIN WHEN COMPARED WITH PATIENTS WITHOUT THYREOPATHIES (1500 (8722336) VS 513 (370698) G/L; P0.0001). PATIENTS WITH FERRITIN VALUES ABOVE 1800G/L EXPERIENCED A SIGNIFICANTLY FASTER EVOLUTION TO ENDPOINT (LOG-RANK ((2)): 7.7; P=0.005). Ferritin predicted high risk of thyroid dysfunction independently of confounding factors (hazard ratio: 1.20; P<0.0001). The intensification of chelation therapy led to an amelioration of thyroid function., Conclusions: Ferritin represents a prognostic marker for βT patients and a predictive factor for progression to thyroid dysfunction. Intensive chelation therapy allows the prevention and reversibility of thyroid complications.